Current controversy
Controversies in lung transplantation: management of cytomegalovirus infections

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Risk of cytomegalovirus infection and disease in lung transplant recipients

It is difficult to determine the exact incidence of CMV infection or disease from the published lung transplant literature due to differences in the definition of CMV infection and disease, immunosuppressive protocols, CMV prophylactic regimens, the lack of risk stratification by CMV serostatus, the evolution of monitoring techniques and the duration of follow-up. The reported incidence of CMV infection and disease following lung transplantation in the post-GCV era ranges from 35% to 86% with

Cytomegalovirus and bronchiolitis obliterans syndrome

The major limiting factor for long-term survival after lung transplantation is bronchiolitis obliterans syndrome (BOS). Recognized risk factors for the development of BOS are the number and severity of acute rejection episodes as well as late-occurring episodes. Several studies suggest that CMV pneumonitis and positive CMV serology are risk factors for BOS.2, 11, 12 However, other reports have not found these same associations.13, 14 CMV may induce allograft injury by direct tissue invasion and

Strategies to prevent cytomegalovirus infection

Three potential mechanisms of CMV infection have been recognized: transmission by the donor organ; transmission by blood products; or reactivation of latent virus in the recipient. The presence of antibody to CMV in the recipient, whether endogenous or passively transferred, appears to provide protection against the development of serious and sometimes fatal disease. In the absence of endogenous antibody protection, primary CMV infections, particularly CMV pneumonitis or gastrointestinal

Techniques to monitor for cytomeglovirus infection

Rapid and accurate diagnostic tests are critical for the appropriate management of CMV following lung transplantation. Diagnostic tests for CMV have undergone rapid evolution since the early 1990s. Initially, most programs followed seroconversion as measured by rising antibody titers or surveillance cultures of blood, throat swabs or urine.2 With the exception of blood cultures, these methods were soon found to be insensitive predictors of CMV disease. Many reports soon appeared advocating the

Prophylaxis of cytomegalovirus infection

Prior to the development of effective anti-viral agents, CMV caused illness in the majority of lung transplant recipients, and primary infection in D+/R recipients was associated with severe and often life-threatening disease.7 Following the development of GCV it soon became clear that the short-term morbidity and mortality of CMV infections could be controlled with therapeutic courses of intravenous GCV. Several investigators then sought to determine whether prophylactic use of GCV or other

Pre-emptive therapy

Some centers have advocated pre-emptive therapy based on detection of CMV antigenemia or DNAemia in routinely collected blood samples. The advantage of this strategy is that only high-risk patients are exposed to therapy. This would be expected to be associated with decreased cost and toxicity. Although this approach has been effective in bone marrow transplant patients, it is unclear whether pre-emptive therapy would be efficacious and cost-effective in lung transplant recipients. Several

Treatment

Standard therapy of CMV disease consists of 2 to 3 weeks of IV GCV at a dose of 5 mg/kg twice daily adjusted for renal insufficiency. Of some concern, Duncan et al2 found that treatment with IV GCV as monotherapy did not prevent the long-term sequelae of CMV. Although no controlled trials are available for the use of CMVIg for therapy in organ transplant recipients, many centers add it to their GCV for the treatment of tissue-invasive CMV pneumonia or colitis. Studies in bone marrow transplant

Antiviral resistance

Resistance of CMV to anti-viral agents has been well recognized in the laboratory and clinical setting and is a matter of growing concern in the management of solid organ transplant recipients.40 Infections due to GCV-resistant isolates have been reported in acquired immuno-deficiency syndrome (AIDS) patients, following bone marrow transplants and all solid organ transplants. The incidence of GCV resistance ranges from 2% to 10%, depending on the intensity of the immunosuppressive regimen and

Future directions in cytomegalovirus management

Most of the lung transplant literature to date has dealt with the prevention and treatment of the direct effects of CMV. What remains unanswered, is whether the prevention of the indirect effects of CMV proliferation, in regard to lung transplantation, is the prevention of BOS. It has been suggested that even asymptomatic viral proliferation may be associated with the development of BOS. Therefore, it would seem that prevention of any CMV proliferation, or treatment of asymptomatic infections

Conclusion

Lung transplant programs still need to refine the types of CMV prophylactic strategies that best match individual recipients of seropositive and seronegative allografts and the type of immunosuppression utilized. It seems clear that universal prophylaxis is warranted for high-risk D+/R recipients. However, it remains unclear as to whether R+ recipients are also at higher risk than other solid organ recipients and whether they should receive universal prophylaxis or pre-emptive therapy. The use

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  • Cited by (46)

    • Management strategies for cytomegalovirus infection and disease in solid organ transplant recipients

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      In this regard, kidney recipients with CMV are more likely to develop chronic allograft nephropathy (or tubulointerstitial fibrosis).41 Likewise, lung recipients with CMV are at increased risk of bronchiolitis obliterans,42 whereas heart recipients are at increased risk of accelerated coronary vasculopathy if they developed CMV infection and disease.43,44 CMV disease is associated with increased risk of death after SOT.11,38

    • Infections in heart and lung transplant recipients

      2012, Clinical Microbiology Newsletter
    • Lung Transplant Complications

      2012, Emergency Medicine: Clinical Essentials, SECOND EDITION
    • Recommendations for the use of extended criteria donors in lung transplantation

      2011, Transplantation Proceedings
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      Recipients with positive serology for hepatitis C or those vaccinated for hepatitis B may receive lungs of donors with positive serology for these diseases.24 The use of donors with positive serology (immunoglobulin G) for cytomegalovirus (CMV) in recipients with negative serology increases the risk of infection by CMV.25 There is controversy over the influence of CMV infection to produce an higher incidence of bronchiolitis obliterans.26,27

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